Correlation of rpoB mutations with minimal inhibitory concentration of rifampin and rifabutin in Mycobacterium tuberculosis in an HIV/AIDS endemic setting, South Africa

dc.contributor.authorRukasha, Ivy
dc.contributor.authorSaid, Halima M.
dc.contributor.authorOmar, Shaheed Vally
dc.contributor.authorKoornhof, Hendrik
dc.contributor.authorDreyer, Andries W.
dc.contributor.authorMusekiwa, Alfred
dc.contributor.authorMoultrie, Harry
dc.contributor.authorHoosen, Anwar A.
dc.contributor.authorKaplan, Gilla
dc.contributor.authorFallows, Dorothy
dc.contributor.authorIsmail, Nazir Ahmed
dc.date.accessioned2017-02-08T05:32:08Z
dc.date.available2017-02-08T05:32:08Z
dc.date.issued2016-12-06
dc.description.abstractTreatment of tuberculosis (TB) and HIV co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. Rifabutin (RFB) is an alternative to rifampin (RIF) for TB regimens and is recommended for HIV patients concurrently receiving protease inhibitors because of reduced induction of CYP3A4. This study sought to determine the proportion of RFB susceptible isolates among RIF-resistant strains in a high HIV prevalence setting in South Africa. In addition, the study explored the association between rpoB mutations and minimum inhibitory concentrations (MIC) of RIF and RFB. A total of 189 multidrug resistant (MDR) Mycobacterium tuberculosis isolates from the Centre for Tuberculosis repository were analyzed. The MICs were determined using a MYCOTB Sensititre plate method and the rpoB gene was sequenced. Of the 189 MDR isolates, 138 (73%) showed resistance to both RIF and RFB, while 51 (27%) isolates were resistant to RIF but retained susceptibility to RFB. The S531L was the most frequent rpoB point mutation in 105/189 (56%) isolates, followed by H526Y in 27/189 (14%) isolates. Resistance to both RIF and RFB was found predominantly in association with mutations S531L (91/105, 87%), H526Y (20/27, 74%), and H526D (15/19, 79%), while D516V (15/17, 88%), and L533P (3/4, 75%) were found in RIF-resistant, RFB-susceptible isolates. This study has shown that up to 27% of MDR-TB patients in South Africa may benefit from a treatment regimen that includes RFB.en_ZA
dc.description.departmentMedical Microbiologyen_ZA
dc.description.librarianam2017en_ZA
dc.description.sponsorshipThe research was funded by a grant from the NIH (ROI A180737) to GK which was transferred to DF.en_ZA
dc.description.urihttp://www.frontiersin.orgen_ZA
dc.identifier.citationRukasha I, Said HM, Omar SV, Koornhof H, Dreyer AW, Musekiwa A, Moultrie H, Hoosen AA, Kaplan G, Fallows D and Ismail N (2016) Correlation of rpoB Mutations with Minimal Inhibitory Concentration of Rifampin and Rifabutin in Mycobacterium tuberculosis in an HIV/AIDS Endemic Setting, South Africa. Front. Microbiol. 7:1947. DOI: 10.3389/fmicb.2016.01947.en_ZA
dc.identifier.issn1664-302X
dc.identifier.other10.3389/fmicb.2016.01947
dc.identifier.urihttp://hdl.handle.net/2263/58910
dc.language.isoenen_ZA
dc.publisherFrontiers Research Foundationen_ZA
dc.rights© 2016 Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en_ZA
dc.subjectrpoBen_ZA
dc.subjectRifampicinen_ZA
dc.subjectMinimum inhibitory concentrationen_ZA
dc.subjectHIV/AIDSen_ZA
dc.subjectPoint mutationen_ZA
dc.subjectTuberculosis (TB)en_ZA
dc.subjectRifabutin (RFB)en_ZA
dc.subjectMinimum inhibitory concentrations (MIC)en_ZA
dc.subjectMultidrug-resistant (MDR)en_ZA
dc.subjectMycobacterium tuberculosis (MTB)en_ZA
dc.subjectHuman immunodeficiency virus (HIV)en_ZA
dc.subjectAcquired immune deficiency syndrome (AIDS)en_ZA
dc.subjectSouth Africa (SA)en_ZA
dc.titleCorrelation of rpoB mutations with minimal inhibitory concentration of rifampin and rifabutin in Mycobacterium tuberculosis in an HIV/AIDS endemic setting, South Africaen_ZA
dc.typeArticleen_ZA

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